We have isolated a number of transformation defective large plaque (lp) mutants of adenovirus 2. Some of the lp mutants map within a narrow segment of the viral genome between mp 4.5 to 5.8 and are defective in synthesis of Elb-19K polypeptide. The Ad2 lp mutants resemble the Ad12 cyt mutants which are also transformation defective (Takemori et al., 1968). We propose an indepth investigation of the role of lp+ and cyt+ loci in cellular transformation and in tumorigenesis. We will carry out detailed characterization of the Ad2 lp and Ad12 cyt mutants by physical mapping and complementation analysis. Effect of lp mutation on the cellular parameters such as the loss of cytoskeletal structures, increased secretion of plasminogen activator, and anchorage independence normally associated with transformed cells will be investigated. The role of the lp locus in the initiation or maintenance of transformation will be investigated using ts lp td mutants. We will map the functional domains of Elb-19K essential for cellular transformation and for tumorigenesis. In order to understand the mechanism of Elb-19K induced cellular transformation, we will identify the cellular target proteins associated with 19K and the 19K-mediated modifications of the cellular components.